Table 1.

Summary of useful biomarker terms.

Term	Definition	References
Accuracy	assessed by measuring recovery of the spiked analyte tested in triplicate	21
Anabolic	Synthesis
Catabolic	Degradative
Clinically meaningful limits	the maximum amount of variability in laboratory test results that will not affect patient care	22
Direct Biomarker	Mechanistic, in pathway of disease
Duplicate	quantification of a biomarker from two independent volumes of the same sample for the purposes of assessing precision and variability
ELISA	Enzyme Linked Immunosorbent Assay, an immunological assay technique used primarily for measuring an antigenic region of a protein and making use of an enzyme bonded to an antibody to detect the antigen
Endotype	a subtype of a condition, which is defined by a distinct functional or pathobiological mechanism
Good biomarker practices	Use of best practices in biobanking (including standardized specimen acquisition, storage and preparation, and acquisition of high-quality associated phenotypic data), translational research (standardized and reproducible analytical methods to ensure the results are reproducible and usable) and data stewardship (data are findable, accessible, interoperable and reusable—FAIR)	23
Harmonization	the process of ensuring that the results of different laboratories using different clinical laboratory tests at different times to measure the same substance are equivalent within clinically meaningful limits	22
Indirect Biomarker	An indirect sign of a pathway that is not fundamental to the key disease processes
Invariant	Genetic markers (polymorphisms) in DNA
LOD (limit of detection)	The minimum concentration that can be detected reliably based on a signal-to-noise approach; a signal-to-noise ratio between 2:1 or 3:1 is generally considered acceptable for estimating the detection limit; it is determined as the concentration corresponding to 2-3 standard deviations above the background (zero calibrator). Some assays use Minimal detectable dose (MDD) which is determined by adding two SDs to the mean optical density (OD) value of twenty zero standard replicates and calculating the corresponding concentration. At LOD and LOQ calculations, signal of analyte (S) should be 3 or 10 times of blank signal (N), respectively.	DOI:10.1016/j.jfda.2015.04.009
LOQ (limit of quantification)	The quantification limit of an individual analytical procedure is the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy.
Multiplex	quantification of multiple biomarkers in a single sample volume
Precision	measured using a minimum of five determinations per concentration. The precision determined at each concentration level should not exceed 15% of the coefficient of variation (CV) except for the LLOQ, where it should not exceed 20% of the CV.	21
Singleplex	quantification of a single biomarker
Qualification	providing evidence that biomarker is linked with a certain biological process and clinical endpoint; process applied to a particular biomarker to support its use as a surrogate endpoint in drug discovery, development or post-approval and, where appropriate, in regulatory decision-making	24
Quantification	the act of counting and measuring
Reliability	Reliability tells you how consistently a method measures something. The same method applied to the same sample under the same conditions should yield the same results. If not, the method of measurement may be unreliable.
Reproducibility	assessed by replicate measurements using the assay	21
Singlicate	quantification of a biomarker from a given volume of sample
Stability	Minimal variation under expected sample handling and storage conditions, including, among others, effects of freeze-thaw. For a stable biomarker, a mean value of a minimum of three concentrations in the range of expected study sample concentrations, should be within 15% of the nominal value except at LLOQ, where it should not deviate by more than 20%.	21
Standard curve	Assay standards or calibrators representing serial dilutions of one known concentration of the analyte across a range of concentrations near the expected (but unknown) concentration The concentration of the unknown may be calculated from the mass in the assay
Standardization	the achievement of equivalent results by different clinical laboratory tests conducted by different laboratories using reference samples that can be traced to a reference measurement procedure	22
Surrogate biomarker	A “surrogate marker” can be defined as “a laboratory measurement or physical sign that is used in therapeutic trials as a substitute for a clinically meaningful endpoint that is a direct measure of how a patient feels, functions, or survives and is expected to predict the effect of the therapy.”5 The primary difference between a biomarker and a surrogate marker is that a biomarker is a “candidate” surrogate marker, whereas a surrogate marker is a test used, and taken, as a measure of the effects of a specific treatment. Russell Katz, Biomarkers and Surrogate Markers: An FDA Perspective, NeuroRx 1(2): 189-195, April 2004	http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=534924
Theragnostic	A molecular diagnostic that guides treatment
Validation	The action of proving good technical performance characteristics of an assay, such as, for example, precision, accuracy, detection limit and robustness.	21, 25
Validity	How accurately a method measures something	26
Validity—face validity	The content of the test appears to be suitable to its aims	26
Validity—construct validity	The test measures the concept that it s intended to measure?	26
Validity—content validity	The test is fully representative of what it aims to measure	26
Validity—criterion validity	The results correspond to a different test of the same thing	26
Variant	Dynamic markers such as protein, RNA, and miRNA
‘wet’ and ‘dry’ biomarkers	soluble and insoluble biomarkers